Binary inclusion complexes of diflunisal with β-cyclodextrin and hydroxypropyl-β-cyclodextrin: Preparation and...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Physical Chemistry

Background:

• Poor aqueous solubility and bioavailability limit the therapeutic efficacy of many drugs.
• Diflunisal (DIF) is a non-steroidal anti-inflammatory drug with low aqueous solubility.

Purpose of the Study:

• To investigate the impact of beta-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) on diflunisal (DIF) solubility and dissolution.
• To compare the efficacy of physical mixing and solvent evaporation methods for preparing DIF-cyclodextrin inclusion complexes.

Main Methods:

• Phase solubility studies were conducted to assess solubility enhancement.
• Inclusion complexes were prepared using physical mixing and solvent evaporation at various drug-to-cyclodextrin ratios (1:1, 1:2, 1:4).
• Characterization involved scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD).

Main Results:

• Diflunisal solubility increased with higher concentrations of both βCD and HPβCD.
• The solvent evaporation method resulted in significantly higher DIF solubility compared to physical mixing.
• HPβCD-DIF inclusion complexes exhibited a superior dissolution profile over βCD-DIF complexes.
• FTIR, DSC, and XRD confirmed the successful formation of DIF inclusion complexes, demonstrating enhanced water solubility and drug release.

Conclusions:

• Both βCD and HPβCD effectively enhance the aqueous solubility and dissolution of diflunisal.
• The solvent evaporation method and HPβCD are more effective for preparing inclusion complexes with improved diflunisal solubility and release.
• These findings suggest a promising strategy for improving the bioavailability of poorly soluble drugs like diflunisal.